Background & Aims: Opioids have a role in chronic pain management. However, opioid-induced constipation may cause patients to skip or reduce opioid doses, leading to inadequate pain relief and negatively impacting quality of life. We sought to establish a minimal clinically important difference to understand whether changes in quality of life scores are of value to patients. Methods: Integrated data from the double-blind, controlled, phase 3 COMPOSE-1 and COMPOSE-2 trials of naldemedine in chronic noncancer pain and opioid-induced constipation were used to determine minimal clinically important differences using Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Patients completed the questionnaires (5-point Likert scale; predose, Weeks 2, 4, and 12), kept a daily log of Bowel Movement and Constipation Assessment, and rated satisfaction at end of study. Minimal clinically important differences were computed using an anchor-based method with 6 anchors: 5 from the Bowel Movement and Constipation Assessment and 1 from patient satisfaction. Threshold values for each anchor were set to define responders versus nonresponders based on score definitions. Clinically meaningful cutoff values for changes in PAC-SYM and PAC-QOL scores were determined using receiver operating characteristic curves. Results: Data from 1095 patients (549, naldemedine; 546, placebo) were analyzed. The area under the curve for the receiver operating characteristic curves (ranges, 0.719 to 0.798 for PAC-SYM and 0.734 to 0.833 for PAC-QOL) indicated that both instruments can discriminate responders and nonresponders for each anchor. PAC-SYM cutoff values ranged from −1.04 to −0.83; PAC-QOL cutoff values ranged from −0.93 to −0.82. Conclusions: Based on data derived from the anchor method, reductions in PAC-SYM and PAC-QOL scores of >1.0 in patients with chronic noncancer pain and opioid-induced constipation are clinically meaningful. ClinicalTrials.gov Registration: NCT01965158; NCT01993940.
- Opioid-Related Disorders
ASJC Scopus subject areas